This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We will prepare macromolecular complexes of HIV-1 reverse transcriptase (RT), an essential component in the life cycle of the HIV-1 virus, with nucleic acid and nucleoside and nonnucleoside reverse transcriptase inhibitors. The three dimensional structures of these complexes will be determined by x-ray crystallographic methods. Through these studies we hope to gain a detailed understanding of the fundamental principles underlying inhibition of RT's function and the emergence of resistance to these inhibitors. Ultimately we hope to apply information garnered from our stuctural studies towards the advancement of new and effective treatment stategies in the form of better anti-HIV drugs.